Our research is motivated by the way infectious diseases can cause wildly different outcomes in different people. One of the factors that determines infection severity is what happened in the past – the history of the immune cells that are the front-line defense against the infection. In other words, for immune cells, the past shapes the present. This is similar to how the human response to a given stimulus might differ depending on what had previously happened to us that day. If someone cuts us off on the freeway, we are much more likely to forgive the offense if we are coming back from a relaxing day at the beach than if we are coming off a stressful overnight work shift! Immune cells are no different. Context matters. The past shapes the response to present stimuli.
How past exposures reprogram cells of the innate immune system is known as “trained immunity.” Our research examines the molecular mechanisms of trained immunity and how it contributes to the variable outcomes of infections. We are particularly interested in the mechanisms by which the epigenome of macrophages are reprogrammed by past exposures. How do different ligands produce different epigenomic reprogramming signatures? How do chronic diseases like diabetes alter the epigenetic state of innate immune cells? Our hope is that by better understanding how trained immunity works we will be able to predict which patients are at risk for severe infections and provide our own “training” of the immune system to improve human health.
A selected list of publications:
NFκB dynamics determine the stimulus-specificity of epigenomic reprogramming in macrophages. QJ Cheng, S Ohta, KS Sheu, R Spreafico, A Adelaja, B Taylor, A Hoffmann. Science, 2021 Jun 18.
High dose IFN-beta activates GAF to enhance expression of ISGF3 target genes in MLE12 epithelial cells. K Kishimoto, CL Wilder, J Buchanan, M Nguyen, C Okeke, A Hoffmann, QJ Cheng. 2021. Frontiers in Immunology 12:651254.
An NFκB activity calculator to delineate signaling crosstalk: type I and type II interferon modulate NFκB signaling via distinct mechanisms. S Mitchell, EL Mercado, A Adelaja, J Ho, QJ Cheng, G Ghosh, A Hoffmann. Frontiers in Immunology, 2019 Jun 25.
Sequential conditioning-stimulation reveals distinct gene- and stimulus-specific effects of Type I and II IFN on human macrophage functions. Q Cheng, F Behzadi, S Sen, S Ohta, R Spreafico, R Teles, R Modlin, A Hoffmann. Scientific Reports, 2019 Mar 27.
Duodenoscope-related outbreak of a carbapenem-resistant Klebsiella pneumoniae identified using advanced molecular diagnostics. RM Humphries, S Yang, S Kim, VR Muthusamy, D Russell, A Trout, T Zaroda, QJ Cheng, G Aldrovandi, DZ Uslan, P Hemarajata, Z Rubin. Clin Infect Dis. 2017 Aug 8.
Probing chromatin landscape reveals roles of endocardial TBX20 in septation. CJ Boogerd, I Aneas, N Sakabe, RJ Dirschinger, QJ Cheng, B Zhou, J Chen, MA Nobrega, SM Evans. J Clin Invest. 2016 Jun 27.
Who provides primary care? An assessment of HIV patient and provider practices and preferences. QJ Cheng, EM Engelage, TR Grogan, JS Currier, RM Hoffman. J AIDS Clin Res. 2014 Nov; 5(11).
Characterization of a Y-Family DNA Polymerase eta from the Eukaryotic Thermophile Alvinella pompejana. S Kashiwagi, I Kuraoka, Y Fujiwara, K Hitomi, QJ Cheng, JO Fuss, DS Shin, C Masutani, JA Tainer, F Hanaoka, S Iwai. J. Nucleic Acids 2010, 701472.
XPD helicase structures and activities: insights into the cancer and aging phenotypes from XPD mutations. L Fan, JO Fuss, QJ Cheng, AS Arvai, M Hammel, VA Roberts, PK Cooper, JA Tainer. Cell 2008, 133:789.